Pott Hendrik, Weckler Barbara, Gaffron Swetlana, Martin Roman, Maier Dieter, Alter Peter, Biertz Frank, Speicher Tim, Bertrams Wilhelm, Jung Anna Lena, Laakmann Katrin, Heider Dominik, Wouters Miel, Vogelmeier Claus F, Schmeck Bernd
Department of Medicine, Pulmonary and Critical Care Medicine, Clinic for Airway Infections, University Medical Centre Marburg, Philipps-University Marburg, Marburg, Germany.
Viscovery Gmbh, Vienna, Austria.
Respirology. 2025 Feb;30(2):134-146. doi: 10.1111/resp.14843. Epub 2024 Oct 24.
Chronic obstructive pulmonary disease (COPD) exhibits diverse patterns of disease progression, due to underlying disease activity. We hypothesized that changes in static hyperinflation or KCO % predicted would reveal subgroups with disease progression unidentified by preestablished markers (FEV, SGRQ, exacerbation history) and associated with unique baseline biomarker profiles. We explored 18-month measures of disease progression associated with 18-54-month mortality, including changes in hyperinflation parameters and transfer factor, in a large German COPD cohort.
Analysing data of 1364 patients from the German observational COSYCONET-cohort, disease progression and improvement patterns were assessed for their impact on mortality via Cox hazard regression models. Association of biomarkers and COPD Assessment test items with phenotypes of disease progression or improvement were evaluated using logistic regression and random forest models.
Increased risk of 18-54-month mortality was linked to decrease in KCO % predicted (7.5% increments) and FEV (20 mL increments), increase in RV/TLC (2% increments) and SGRQ (≥6 points), and an exacerbation grade of 2 at 18 months. Decrease in KCO % predicted ≥7.5% and an increase of RV/TLC ≥2% were the most frequent measures of 18-month disease progression occurring in ~52% and ~46% of patients, respectively. IL-6 and CRP thresholds exhibited significant associations with medium- and long-term disease measures.
In a multicentric cohort of COPD, new markers of current disease activity predicted mid-term mortality and could not be anticipated by baseline biomarkers.
由于潜在的疾病活动,慢性阻塞性肺疾病(COPD)呈现出多样的疾病进展模式。我们假设,预计的静态肺过度充气或一氧化碳弥散量百分比(KCO%)的变化将揭示出一些疾病进展亚组,这些亚组无法通过预先设定的标志物(第一秒用力呼气容积[FEV]、圣乔治呼吸问卷[SGRQ]、急性加重病史)识别,并且与独特的基线生物标志物谱相关。我们在一个大型德国COPD队列中,探讨了与18至54个月死亡率相关的18个月疾病进展指标,包括肺过度充气参数和肺弥散功能的变化。
分析来自德国观察性COSYCONET队列的1364例患者的数据,通过Cox风险回归模型评估疾病进展和改善模式对死亡率的影响。使用逻辑回归和随机森林模型评估生物标志物和COPD评估测试项目与疾病进展或改善表型的关联。
18至54个月死亡率增加的风险与预计的KCO%降低(增加7.5%)、FEV降低(增加20毫升)、残气量/肺总量(RV/TLC)增加(增加2%)、SGRQ增加(≥6分)以及18个月时急性加重分级为2级有关。预计的KCO%降低≥7.5%和RV/TLC增加≥2%是18个月疾病进展最常见的指标,分别发生在约52%和约46%的患者中。白细胞介素-6(IL-6)和C反应蛋白(CRP)阈值与中长期疾病指标存在显著关联。
在一个多中心的COPD队列中,当前疾病活动的新标志物可预测中期死亡率,且无法通过基线生物标志物进行预测。